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1.
Organ Transplantation ; (6): 90-101, 2024.
Artículo en Chino | WPRIM | ID: wpr-1005238

RESUMEN

Objective To screen key autophagy-related genes in alcoholic hepatitis (AH) and investigate potential biomarkers and therapeutic targets for AH. Methods Two AH gene chips in Gene Expression Omnibus (GEO) and autophagy-related data sets obtained from MSigDB and GeneCards databases were used, and the key genes were verified and obtained by weighted gene co-expression network analysis (WGCNA). The screened key genes were subject to gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI) and immune infiltration analyses. Messenger RNA (mRNA)- microRNA (miRNA) network was constructed to analyze the expression differences of key autophagy-related genes during different stages of AH, which were further validated by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) in the liver tissues of AH patients and mice. Results Eleven autophagy-related genes were screened in AH (EEF1A2, CFTR, SOX4, TREM2, CTHRC1, HSPB8, TUBB3, PRKAA2, RNASE1, MTCL1 and HGF), all of which were up-regulated. In the liver tissues of AH patients and mice, the relative expression levels of SOX4, TREM2, HSPB8 and PRKAA2 in the AH group were higher than those in the control group. Conclusions SOX4, TREM2, HSPB8 and PRKAA2 may be potential biomarkers and therapeutic targets for AH.

2.
Chinese Journal of Rehabilitation Theory and Practice ; (12): 217-222, 2024.
Artículo en Chino | WPRIM | ID: wpr-1013380

RESUMEN

ObjectTo explore the risk factors related to the intensity of post-stroke depression in patients with cerebral infarction during hospitalization in the rehabilitation department. MethodsThe hospital consultation records of cerebral infarction patients in Beijing Bo'ai Hospital from December, 2019 to February, 2023 were reviewed from the hospital information system, and those who were diagnosed as depression visited the department of psychology were selected. It was collected including general information of sexes, ages, education levels, matrimony; medical features of course, location, affected side, sensory disorders, aphasia, agrypnia, dysphagia, hand-shoulder syndrome, constipation; functioning of muscle strength and Brunnstrom stages; and scores of Mini-Mental State Examination (MMSE), National Institutes of Health Stroke Scale (NIHSS), Fugl-Meyer Assessment (FMA), Fugl-Meyer Assessment-Balance (FMA-B), modified Barthel Index (MBI) and Hamilton Depression Scale (HAMD). Patients with HAMD scores ≤ 20 were as the low group, and those > 20 were as the high group. ResultA total of 2 403 hospitalized stroke patients were included, out of which 269 patients with cerebral infarction were diagnosed as depression and visited the department of psychology; while 103 cases were in the low group and 166 cases were in the high group. The incidence of constipation was less, and the incidence of dysphagia and shoulder-hand syndrome was higher in the high group (χ2 > 5.379, P < 0.05), with weaker strength of iliopsoas muscle and quadriceps muscle, earlier of Brunnstrom stage of lower extremities and hands, and worse scores of NIHSS, MMSE, FMA, FMA-B and MBI (|Z| > 2.020, t > 2.171, P < 0.05). Logistic regression showed that constipation (OR = 0.435), quadriceps muscle strength (OR = 0.782) and dysphagia (OR = 2.602) related to the intensity of post-stroke depression in convalescent patients (P < 0.05). ConclusionPost-stroke dysphagia and poor quadriceps muscle strength may exacerbate post-stroke depression; however, constipation may not.

3.
Acta Pharmaceutica Sinica B ; (6): 170-189, 2024.
Artículo en Inglés | WPRIM | ID: wpr-1011231

RESUMEN

Tumor vaccine is a promising strategy for cancer immunotherapy by introducing tumor antigens into the body to activate specific anti-tumor immune responses. Along with the technological breakthroughs in genetic engineering and delivery systems, messenger ribonucleic acid (mRNA) technology has achieved unprecedented development and application over the last few years, especially the emergency use authorizations of two mRNA vaccines during the COVID-19 pandemic, which has saved countless lives and makes the world witness the powerful efficacy of mRNA technology in vaccines. However, unlike infectious disease vaccines, which mainly induce humoral immunity, tumor vaccines also need to activate potent cellular immunity to control tumor growth, which creates a higher demand for mRNA delivery to the lymphatic organs and antigen-presenting cells (APCs). Here we review the existing bottlenecks of mRNA tumor vaccines and advanced nano-based strategies to overcome those challenges, as well as future considerations of mRNA tumor vaccines and their delivery systems.

4.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 24-31, 2023.
Artículo en Chino | WPRIM | ID: wpr-996501

RESUMEN

Colorectal cancer is one of the most common malignant tumors of digestive tract. In 2020, 1.93 million new cases of colorectal cancer were diagnosed globally, ranking third in the global incidence spectrum, and 930 000 new deaths were reported, ranking second in the global cause of death spectrum. Meanwhile, the medical cost of metastatic colorectal cancer is the highest among all stages. A large number of studies have demonstrated that traditional Chinese medicine(TCM) treatment can bring clinical benefits to patients with metastatic colorectal cancer with unique efficacy. In order to further standardize the TCM diagnosis and treatment for metastatic colorectal cancer and improve the level of TCM diagnosis and treatment, Xiyuan Hospital, China Academy of Chinese Medical Sciences, together with other relevant units in China, according to the guideline development process of the World Health Organization Handbook for Guideline Development and the relevant requirements of the Clinical Evidence Grading Criteria on TCM Based on Evidence Body, the Regulations for Group Standards of China Association of Chinese Medicine and others, combined with the characteristics of TCM diagnosis and treatment and the actual situation in China, the Guidelines for TCM Diagnosis and Treatment of Metastatic Colorectal Cancer was developed in accordance with the Catalogue of TCM Diagnosis and Treatment Plans for 105 Diseases in 24 Specialties issued by Department of Medical Administration of National Administration of TCM.

5.
Chinese Journal of Digestive Surgery ; (12): 226-229, 2023.
Artículo en Chino | WPRIM | ID: wpr-990632

RESUMEN

It is well known that Tokyo University Hospital (TUH) is one of the most famous medical centers around the world in Japan. Among several departments in TUH, the Department of Hepatobiliary-Pancreatic Surgery and Artificial Organ and Transplantation Division are representative predominant divisions, which have high-quality diagnostic and treatment service systems being at the leading position in the world. The authors visit the Department of Hepatobiliary-Pancreatic Surgery and Artificial Organ and Transplantation Division in 2022. When studying and working in TUH, the authors make a multi-angle comparisons of the development status and technical levels of hepatobiliary and pancreatic surgery among TUH, western countries and China. It aims to share and exchange with fellow surgeons at home and abroad, and bring benefits or enlightenment to the professional advancement of them.

6.
Chinese Journal of Digestive Surgery ; (12): 160-166, 2023.
Artículo en Chino | WPRIM | ID: wpr-990623

RESUMEN

The hepatic caudate lobe is located in the deep back area of the liver. Due to the unique anatomical position of hepatic caudate lobe, surgical treatment for tumor of hepatic caudate lobe is particularly difficult. Non-surgical treatment, such as ablation, transarterial embolization, etc, is also challenging for tumor of hepatic caudate lobe, and the therapeutic effect is inferior to that of surgery. Therefore, surgical resection is the only treatment for tumor of hepatic caudate lobe. The authors discuss the research history of hepatic caudate lobe, the problems of laparoscopic technique in hepatic caudate lobe resection, etc, in order to provide a theoretical basis for improving the concept of accuracy of laparoscopic caudate lobectomy.

7.
International Journal of Cerebrovascular Diseases ; (12): 192-196, 2023.
Artículo en Chino | WPRIM | ID: wpr-989211

RESUMEN

Objective:To investigate the effects of cognitive types on dual-task paradigm gait performance in patients with stroke.Method:Using a cross-sectional study design, patients with stroke were trained with single task walking and dual-task walking with four different cognitive tasks (spontaneous speech [SS], serial counting backward [SCB], word list generation (WLG), and auditory Stroop [AS]). A three-dimensional gait and motion analysis system were used to record and analyze gait data, and calculate dual-task effect (DTE) for different cognitive tasks, and compare the differences in spatiotemporal parameters and DTE of gait analysis under different states.Results:A total of 35 patients with stroke (aged 61.0±2.5 years) were included, among which 27 were males (77.1%). There were 25 patients with ischemic stroke (71.4%) and 10 patients with hemorrhagic stroke (28.6%). Compared with single task walking, patients had decreased gait speed, shorter step length on the affected side, and a larger support phase ratio of the unaffected to the affected side during SCB dual task and SS dual task (all P<0.05), and the difference was more obvious during SCB dual task ( P<0.05). Compared with single task walking, patients had a reduced swing phase ratio of the unaffected to the affected side during SCB dual task (all P<0.05). The DTEs of gait speed, step length of the affected side, and the support phase ratio of the unaffected to the affected side during SCB dual task and SS dual task were significantly greater than those during WLG dual task and AS dual task ( P<0.05). The DTEs of gait speed and step length of the affected side during SCB dual task were significantly greater than that during SS dual task (all P<0.05). The DTE of the swing phase ratio of the unaffected to the affected side during SCB dual task was significantly greater than that during other types of cognitive tasks (all P<0.05). Conclusion:Different cognitive tasks had different effects on gait performance during dual-task walking in patients with stroke, and the degree of dual-task interference was associated with specific task types.

8.
Chinese Journal of Otorhinolaryngology Head and Neck Surgery ; (12): 544-551, 2023.
Artículo en Chino | WPRIM | ID: wpr-986925

RESUMEN

Objective: To explore the diagnosis, surgical management and outcome of jugular foramen chondrosarcoma (CSA). Methods: Fifteen patients with jugular foramen CSA hospitalized in the Department of Otorhinolaryngology Head and Neck Surgery of Chinese PLA General Hospital from December 2002 to February 2020 were retrospectively collected,of whom 2 were male and 13 were female, aging from 22 to 61 years old. The clinical symptoms and signs, imaging features, differential diagnosis, surgical approaches, function of facial nerve and cranial nerves IX to XII, and surgical outcomes were analyzed. Results: Patients with jugular foramen CSA mainly presented with facial paralysis, hearing loss, hoarseness, cough, tinnitus and local mass. Computed tomography (CT) and magnetic resonance (MR) could provide important information for diagnosis. CT showed irregular destruction on bone margin of the jugular foramen. MR demonstrated iso or hypointense on T1WI, hyperintense on T2WI and heterogeneous contrast-enhancement. Surgical approaches were chosen upon the sizes and scopes of the tumors. Inferior temporal fossa A approach was adopted in 12 cases, inferior temporal fossa B approach in 2 cases and mastoid combined parotid approach in 1 case. Five patients with facial nerve involved received great auricular nerve graft. The House Brackmann (H-B) grading scale was used to evaluate the facial nerve function. Preoperative facial nerve function ranked grade Ⅴ in 4 cases and grade Ⅵ in 1 case. Postoperative facial nerve function improved to grade Ⅲ in 2 cases and grade Ⅵ in 3 cases. Five patients presented with cranial nerves Ⅸ and Ⅹ palsies. Hoarseness and cough of 2 cases improved after operation, while the other 3 cases did not. All the patients were diagnosed CSA by histopathology and immunohistochemistry, with immunohistochemical staining showing vimentin and S-100 positive, but cytokeratin negative in tumor cells. All patients survived during 28 to 234 months' follow-up. Two patients suffered from tumor recurrence 7 years after surgery and received revision surgery. No complications such as cerebrospinal fluid leakage and intracranial infection occurred after operation. Conclusions: Jugular foramen CSA lacks characteristic symptoms or signs. Imaging is helpful to differential diagnosis. Surgery is the primary treatment of jugular foramen CSA. Patients with facial paralysis should receive surgery in time as to restore the facial nerve. Long-term follow-up is necessary after surgery in case of recurrence.


Asunto(s)
Humanos , Masculino , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Parálisis Facial/etiología , Diagnóstico Diferencial , Foramina Yugular , Estudios Retrospectivos , Tos , Ronquera , Recurrencia Local de Neoplasia , Condrosarcoma/cirugía
9.
Journal of Geriatric Cardiology ; (12): 577-585, 2023.
Artículo en Inglés | WPRIM | ID: wpr-1010185

RESUMEN

OBJECTIVE@#To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score.@*METHODS@#The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion.@*RESULTS@#Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m2, NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m2, albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01).@*CONCLUSIONS@#The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.

10.
Chinese Acupuncture & Moxibustion ; (12): 191-196, 2023.
Artículo en Chino | WPRIM | ID: wpr-969970

RESUMEN

OBJECTIVE@#To investigate the effects of umbilical moxibustion therapy on phobic behavior and the contents of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in different brain regions of the stress-model rats and explore the potential mechanism of umbilical moxibustion on phobic behavior.@*METHODS@#Among 50 Wistar male rats, 45 rates were selected and randomly divided into a control group, a model group and an umbilical moxibustion group, 15 rats in each one; and the rest 5 rats were used for preparing the model of electric shock. The bystander electroshock method was adopted to prepare phobic stress model in the model group and the umbilical moxibustion group. After modeling, the intervention with umbilical moxibustion started in the umbilical moxibustion group, in which, the ginger-isolated moxibustion was applied at "Shenque" (CV 8), once daily, 2 cones for 20 min each time, for consecutively 21 days. After modeling and intervention completed, the rats in each group were subjected to the open field test to evaluate the state of fear. After intervention, the Morris water maze test and fear conditioning test were performed to evaluate the changes in learning and memory ability and the state of fear. Using high performance liquid chromatography (HPLC), the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were determined.@*RESULTS@#Compared with the control group, the horizontal and vertical activity scores were lower (P<0.01), the number of stool particles was increased (P<0.01), the escape latency was prolonged (P<0.01), the times of target quadrant were reduced (P<0.01), and the freezing time was prolonged (P<0.05) in the rats of the model group. The horizontal and vertical activity scores were increased (P<0.05), the number of stool particles was reduced (P<0.05), the escape latency was shortened (P<0.05, P<0.01), the times of target quadrant were increased (P<0.05), and the freezing time was shortened (P<0.05) in the rats of the umbilical moxibustion group when compared with the model group. The trend search strategy was adopted in the control group and the umbilical moxibustion group, while the random search strategy was used in rats of the model group. Compared with the control group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were reduced (P<0.01) in the model group. In the umbilical moxibustion group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were increased (P<0.05, P<0.01) when compared with the model group.@*CONCLUSION@#Umbilical moxibustion can effectively relieve the state of fear and learning and memory impairment of phobic stress model rats, which may be related to the up-regulation of contents of brain neurotransmitters, i.e. NE, DA, and 5-HT.


Asunto(s)
Ratas , Masculino , Animales , Moxibustión , Ratas Sprague-Dawley , Ratas Wistar , Serotonina , Hipocampo , Dopamina , Norepinefrina , Neurotransmisores
11.
Chinese Medical Journal ; (24): 2948-2959, 2023.
Artículo en Inglés | WPRIM | ID: wpr-1007725

RESUMEN

BACKGROUND@#Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine can induce a potent cellular and humoral immune response to protect against SARS-CoV-2 infection. However, it was unknown whether SARS-CoV-2 vaccination can induce effective natural killer (NK) cell response in people living with human immunodeficiency virus (PLWH) and healthy individuals.@*METHODS@#Forty-seven PLWH and thirty healthy controls (HCs) inoculated with SARS-CoV-2 inactivated vaccine were enrolled from Beijing Youan Hospital in this study. The effect of SARS-CoV-2 vaccine on NK cell frequency, phenotype, and function in PLWH and HCs was evaluated by flow cytometry, and the response of NK cells to SARS-CoV-2 Omicron Spike (SARS-2-OS) protein stimulation was also evaluated.@*RESULTS@#SARS-CoV-2 vaccine inoculation elicited activation and degranulation of NK cells in PLWH, which peaked at 2 weeks and then decreased to a minimum at 12 weeks after the third dose of vaccine. However, in vitro stimulation of the corresponding peripheral blood monocular cells from PLWH with SARS-2-OS protein did not upregulate the expression of the aforementioned markers. Additionally, the frequencies of NK cells expressing the activation markers CD25 and CD69 in PLWH were significantly lower than those in HCs at 0, 4 and 12 weeks, but the percentage of CD16 + NK cells in PLWH was significantly higher than that in HCs at 2, 4 and 12 weeks after the third dose of vaccine. Interestingly, the frequency of CD16 + NK cells was significantly negatively correlated with the proportion of CD107a + NK cells in PLWH at each time point after the third dose. Similarly, this phenomenon was also observed in HCs at 0, 2, and 4 weeks after the third dose. Finally, regardless of whether NK cells were stimulated with SARS-2-OS or not, we did not observe any differences in the expression of NK cell degranulation markers between PLWH and HCs.@*CONCLUSION@#s:SARS-CoV-2 vaccine elicited activation and degranulation of NK cells, indicating that the inoculation of SARS-CoV-2 vaccine enhances NK cell immune response.


Asunto(s)
Humanos , Vacunas contra la COVID-19/uso terapéutico , COVID-19 , SARS-CoV-2 , Células Asesinas Naturales , Infecciones por VIH , Anticuerpos Antivirales
12.
Chinese Medical Journal ; (24): 2938-2947, 2023.
Artículo en Inglés | WPRIM | ID: wpr-1007713

RESUMEN

BACKGROUND@#T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines.@*METHODS@#Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT + CD4 + and TIGIT + CD8 + T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose.@*RESULTS@#Compared to that in HCs, the frequency of TIGIT + CD8 + T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT + CD8 + T cells also increased. A decrease in the ratio of both T naïve (T N ) and central memory (T CM ) cells among TIGIT + CD8 + T cells and an increase in the ratio of the effector memory (T EM ) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT + CD8 + T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT + CD8 + T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT + CD8 + T cells in PLWH were significantly weaker than those of TIGIT - CD8 + T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT + CD8 + T cells and TIGIT - CD8 + T cells was insignificant at 4W and 12W, except at 0W.@*CONCLUSIONS@#TIGIT expression on CD8 + T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8 + T cells, thereby enhancing the effectiveness of vaccination.


Asunto(s)
Humanos , Anticuerpos Antivirales , Linfocitos T CD8-positivos , COVID-19/complicaciones , Vacunas contra la COVID-19/inmunología , Infecciones por VIH/complicaciones , Receptores Inmunológicos , SARS-CoV-2
13.
Chinese Medical Journal ; (24): 2658-2667, 2023.
Artículo en Inglés | WPRIM | ID: wpr-1007711

RESUMEN

Although antiretroviral therapy (ART) can reduce the viral load in the plasma to undetectable levels in human immunodeficiency virus (HIV)-infected individuals, ART alone cannot completely eliminate HIV due to its integration into the host cell genome to form viral reservoirs. To achieve a functional cure for HIV infection, numerous preclinical and clinical studies are underway to develop innovative immunotherapies to eliminate HIV reservoirs in the absence of ART. Early studies have tested adoptive T-cell therapies in HIV-infected individuals, but their effectiveness was limited. In recent years, with the technological progress and great success of chimeric antigen receptor (CAR) therapy in the treatment of hematological malignancies, CAR therapy has gradually shown its advantages in the field of HIV infection. Many studies have identified a variety of HIV-specific CAR structures and types of cytolytic effector cells. Therefore, CAR therapy may be beneficial for enhancing HIV immunity, achieving HIV control, and eliminating HIV reservoirs, gradually becoming a promising strategy for achieving a functional HIV cure. In this review, we provide an overview of the design of anti-HIV CAR proteins, the cell types of anti-HIV CAR (including CAR T cells, CAR natural killer cells, and CAR-encoding hematopoietic stem/progenitor cells), the clinical application of CAR therapy in HIV infection, and the prospects and challenges in anti-HIV CAR therapy for maintaining viral suppression and eliminating HIV reservoirs.


Asunto(s)
Humanos , Inmunoterapia Adoptiva , Infecciones por VIH/terapia , VIH-1
14.
Frontiers of Medicine ; (4): 1170-1185, 2023.
Artículo en Inglés | WPRIM | ID: wpr-1010819

RESUMEN

OX40 is a costimulatory receptor that is expressed primarily on activated CD4+, CD8+, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.


Asunto(s)
Ratones , Animales , Receptores del Factor de Necrosis Tumoral/fisiología , Receptores OX40 , Glicoproteínas de Membrana , Ligandos , Anticuerpos Monoclonales/farmacología , Antineoplásicos/farmacología
15.
Journal of Sun Yat-sen University(Medical Sciences) ; (6): 718-720, 2023.
Artículo en Chino | WPRIM | ID: wpr-979228

RESUMEN

A new study in Cell from Ivan de Araujo and colleagues reported that intestinal GLP-1 acts on an inter-organ sympathetic neural circuit that induces appetite suppression. This study revealed that GLP-1, secreted by ileal L cells, sensing by intestinal myenteric layer intestinofugal neurons activated a sympatho-gastro-spinal-reticular-hypothalamic pathway involved in appetite suppression, linking stomach distention to craniofacial programs for food rejection. These molecularly indentified, delimited enteric circuits may be targeted to ameliorate the abdominal bloating and loss of appetite typical of gastric motility disorders.

16.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 142-148, 2023.
Artículo en Chino | WPRIM | ID: wpr-973143

RESUMEN

ObjectiveTo investigate the mechanism of Renshen Guben oral liquids(RGOL) in treatment of mice with renal fibrosis based on metabolomics and network pharmacology. MethodC57BL/6 mice were randomly divided into control group, model group and RGOL group, 12 mice in each group. Except for the control group, mice in the other groups were induced into unilateral ureteral obstruction(UUO) model by UUO. After preparation of the model, an aqueous solution of 4.2 g·kg-1 extract powder was administered by gavage to RGOL group for 14 d, and an equal amount of distilled water was administered by gavage to the control and model groups. After the last administration on the 14th day, urine was collected and detected by ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QQQ-MS/MS) with 0.1% formic acid aqueous solution as mobile phase A, and acetonitrile-isopropanol(70∶30) as mobile phase B for gradient elution(0-1 min, 5%B; 1-5 min, 5%-30%B; 5-9 min, 30%-50%B; 9-11 min, 50%-78%B; 11-13.5 min, 78%-95%B; 13.5-14 min, 95%-100%B; 14-16 min, 100%B; 16-16.1 min, 100%-5%B; 16.1-18 min, 5%B), column temperature of 40 ℃, flow rate of 0.4 mL·min-1, electrospray ionization(ESI), collection range of m/z 50-900. Through network pharmacology, the targets of components in RGOL and the targets of renal fibrosis were analyzed interactively, and the key components and key targets were screened by network topology analysis, and DAVID platform was used to predict the signaling pathways of RGOL for the treatment of renal fibrosis. ResultA total of 7 differential metabolites involving 8 metabolic pathways were identified in RGOL for the treatment of renal fibrosis. The network pharmacology revealed that 36 key components in RGOL were related to 7 differential metabolites, mainly ginsenosides, notoginsenosides and nucleotides. Based on the herbs-components-targets-pathways network, a total of 23 key targets related to the treatment of renal fibrosis by RGOL were highlighted, which together with the differential metabolites were involved in linoleic acid metabolism, arginine biosynthesis, tricarboxylic acid cycle(TCA), arginine and proline metabolism and other pathways. ConclusionBased on metabolomics and network pharmacology, this study preliminarily identified 7 differential metabolites, 36 potential pharmacodynamic components and 23 key targets and 4 key pathways in RGOL for the treatment of renal fibrosis, providing an experimental basis for the clinical application and mechanism study of this preparation.

17.
Chinese Journal of Rehabilitation Theory and Practice ; (12): 249-255, 2023.
Artículo en Chino | WPRIM | ID: wpr-971864

RESUMEN

ObjectiveTo explore the effect of low frequency or high frequency repetitive transcranial magnetic stimulation (rTMS) on right Broca's homologue in stroke patients with nonfluent aphasia. MethodsFrom January, 2019 to August, 2022, 80 inpatients in Beijing Bo'ai Hospital were randomly divided into control group (n = 20), sham stimulation group (n = 20), low-frequency (1 Hz) rTMS (LF-rTMS) group (n = 20) and high-frequency (10 Hz) rTMS (HF-rTMS) group (n = 20). All the patients received routine language therapy. LF-rTMS group and HF-rTMS group received ten days of rTMS (1 Hz or 10 Hz), and the sham group received ten days of sham rTMS. The Western Aphasia Battery (WAB) was used to evaluate the language function before, after treatment, and two months after treatment. ResultsBefore treatment, there was no significant difference in the scores of WAB among four groups (P > 0.05). All the scores improved in the four groups immediately after treatment and two months after treatment (P < 0.05). Compared with immediately after treatment, all the scores of WAB improved in LF-rTMS group (P < 0.05), and the scores of recall, name and aphasia quotient (AQ) improved in HF-rTMS group (P < 0.05) two months after treatment. Immediately after treatment, the scores of content and fluency, auditory comprehension and AQ were higher in LF-rTMS group than in HF-rTMS group (P < 0.05). Two months after treatment, the scores of content and fluency were higher in LF-rTMS group than in HF-rTMS group (P < 0.05). ConclusionBoth 1 Hz and 10 Hz rTMS could improve the language function of stroke patients with nonfluent aphasia, especially 1 Hz.

18.
Chinese Journal of Surgery ; (12): 114-119, 2023.
Artículo en Chino | WPRIM | ID: wpr-970194

RESUMEN

Objective: To examine the application of volume replacement techniques in breast conserving surgery for breast cancer. Methods: The clinic data of 76 breast cancer patients underwent a breast conserving surgery with volume replacement techniques at the Breast Center, Beijing Tongren Hospital, from June 2019 to June 2021 were analyzed retrospectively. All patients were female, aged (42.6±6.4) years (range: 32 to 56 years). Tumor staging inlcuded stage ⅡA in 36 cases, stage ⅡB in 24 cases, stage ⅢA in 12 cases, stage ⅢB in 4 cases. Three types of techniques included the lateral thoracic adipofascial flaps in 47 cases, the upper abdominal wall adipofascial flaps in 22 cases and the latissimus dorsi myocutaneous flap in 7 cases. The specimen volume of tumor expansion resection in breast conserving surgery was measured, while the operative time used for volume replacement techniques, postoperative drainage retention time, postoperative complications and patients' satisfaction with the breast shape were recorded. Results: The specimen volume of tumor was (100.9±24.2) ml (range: 55 to 157 ml) in lateral thoracic adipofascial flap group, (88.4±14.5) ml (67 to 118 ml) in upper abdominal wall adipofascial flap group, (179.7±22.9) ml (range: 155 to 220 ml) in latissimus dorsi myocutaneous flap group. The operative time used to restore the breast shape of the three groups were (52.9±9.0) minutes (range: 45 to 70 minutes), (63.2±8.8) minutes (range: 50 to 70 minutes) and (99.3±3.4) minutes (range: 95 to 105 minutes), respectively. The postoperative drainage retention times of the three groups were (8.6±1.2) days (range: 7 to 10 days), (9.4±0.9) days (range: 8 to 10 days) and (11.4±1.3) days (range: 10 to 13 days), respectively. All the 76 patients were evaluated for their satisfaction with the cosmetic outcomes, 64 patients (84.2%) were strongly satisfied and 12 patients (15.8%) were generally satisfied. The postoperative complications included fat liquefaction in 6 cases (2 cases in the lateral thoracic adipofascial flap group and 4 cases in the upper abdominal adipofascial flap group) and seroma in 4 cases (each 2 cases in the lateral thoracic adipofascial flap group and the latissimus dorsi myocutaneous flap group). Conclusions: For patients with large tissue loss during breast conserving surgery, the corresponding volume replacement techniques, including lateral thoracic adipofascial flaps, upper abdominal wall adpofascial flaps and latissimus dorsi myocutaneous flaps, should be reasonably selected for repair according to the tumor site and the size of the intraoperative breast loss, which can ensure the original volume and shape of the breast, with controllable postoperative complications.


Asunto(s)
Humanos , Femenino , Masculino , Neoplasias de la Mama/cirugía , Mastectomía Segmentaria , Estudios Retrospectivos , Mama , Complicaciones Posoperatorias
19.
Chinese Journal of Rehabilitation Theory and Practice ; (12): 608-614, 2023.
Artículo en Chino | WPRIM | ID: wpr-975148

RESUMEN

ObjectiveTo explore sleep disturbance in preschool children with autism spectrum disorder (ASD) and analyze the relationship between sleep disturbance and social behavior. MethodsFrom December, 2020 to December, 2022, 221 preschool children with ASD from Beijing Bo'ai Hospital and other two institutes, and 246 healthy preschool children socially recruited were investigated with Children's Sleep Habits Questionnaire (CSHQ). A total of 47 ASD children and 47 healthy children were selected from them to wear a sleep monitoring watch for seven days, while the ASD children were evaluated with Gesell Development Diagnosis Scale (GDDS), Psychoeducational Profile-Third Edition (PEP-3), Autism Diagnostic Observation Schedule-2 (ADOS), Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS) and Social Responsiveness Scale (SRS). ResultsAll the factor-scores were more in the ASD children than in the healthy children (t > 2.491, P < 0.05), except that of daytime sleepiness. The prevalence of sleep disturbance (CSHQ ≥ 41) was 89.6% in ASD children, which was more than that of the healthy children (76.8%) (χ2 = 13.360, P < 0.001). The sleep problems in ASD children included bedtime resistance, sleep anxiety, sleep duration, sleep onset delay, parasomnias and sleep disordered breathing. ASD children were shorter in total bedtime, shorter in total sleep time, longer in sleep latency, longer in awake time and lower in sleep efficiency (|t| > 2.001, P < 0.05), compared with those of healthy children. For ASD children, the total bedtime negatively correlated with GDDS-language, PEP-3-expressive language, PEP-3-communication and PEP-3-maladaptive behaviors (r < -0.300, P < 0.05); the sleep efficiency negatively correlated with total score of CARS (r = -0.365, P < 0.05); sleep latency correlated with GDDS-social, PEP-3-cognitive, PEP-3-expressive language, PEP-3-receptive language, PEP-3-visual-motor imitation, PEP-3-characteristic verbal behaviors, PEP-3-communication, original score of ADOS, ADOS-social affect, and total score of CARS (|r| > 2.90, P < 0.05); and total awake time positively correlated with total score of CARS (r = 0.406, P < 0.05). ConclusionSleep disturbance is prevalent and various in preschool ASD children, and influence their social behaviors.

20.
Chinese Journal of Rehabilitation Theory and Practice ; (12): 510-515, 2023.
Artículo en Chino | WPRIM | ID: wpr-975133

RESUMEN

ObjectiveTo investigate the relationship among spontaneous turning direction, balance ability and fall risk in patients with stroke during walking. MethodsFrom December, 2021 to November, 2022, 94 patients with stroke were recruited from Beijing Bo'ai Hospital. They were assessed with simple Timed 'Up and Go' Test (TUGT, TUGT1), TUGT with a cup in hand (TUGT2), and TUGT with calculation task (TUGT3). The spontaneous turning directions at the turn point were recorded, and the patients were divided into no-same group (n = 34) and same group, and the same group was further divided into affected group (n = 33) and unaffected group (n = 27), according to the spontaneous turning direction. After a spontaneous turning of each TUGT, the patients were asked to finish another TUGT turning to the opposite direction. And then, they were assessed with single leg standing test, Functional Reach Test (FRT), 360° turning test and the Morse Fall Scale (MFS). ResultsThere were the most patients with left hemiplegia in the affected group (χ2 = 7.995, P < 0.05). The time of TUGT1, TUGT2 and TUGT3 was the most in the affected group and the least in the unaffected group (F > 4.009, P < 0.05), and it was more in the affected group than in the unaffected group as post-hoc test (P < 0.05). The one leg standing time (H = 9.403, P = 0.009) and FRT distance (F = 4.300, P = 0.016) were the least in the affected group and the most in the unaffected group, and it was less in the affected group than in the unaffected group as post-hoc test (P < 0.05). The turning time (F = 4.134, P = 0.019) and turning steps (F = 5.611, P = 0.003) were the most in the affected group and the least in the unaffected group, and it was more in the affected group than in the unaffected group as post-hoc test (P < 0.05). The score of MFS was the most in the affected group and the least in the unaffected group (H = 8.192, P = 0.017), and it was more in the affected group than in the unaffected group as post-hoc test (P < 0.05). ConclusionThe stroke patients spontaneously turning to the affected side during walking usually are poorer in balance function, and in a risk of fall.

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